Neuropsychiatric Functioning in CDLS: A Detailed Phenotype and Genotype Correlation

Abstract Background: Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder and its phenotype clinical expression is widely variable. Despite the growing interest on genotype-phenotype correlations and on behaviour phenotype of genetic syndromes, specific studies in CdLS cohorts evaluating the correlations between genotype and neurodevelopmental characteristics, Behaviour and communicative aspects are limited, most of these studies are descriptive and there is a lack of specific assessment protocols.Methods: Neurodevelopmental and Behavioural phenotype of all the patients (N = 38) was assessed using a specific neuropsychiatric protocol, concerning Intellectual Quotient (IQ), General Quotient of Development (GQ), communicative skills, behavioural aspects and adaptive behaviour based on direct and indirect evaluation. Subsequently, we searched for possible genotype–phenotype correlations comparing individuals with NIPBL variants (CdLS NIPBL mutated group) and patients with negative molecular results (CdLS clinical diagnosis group). Results: The first part of the study showed a higher percentage of subjects with normal Intellectual Quotient (IQ) and Borderline Intellectual Functioning if compared with previous data; adaptive skills were lower than expected for age in all participants and the weakest areas were Socialization, Motor Skills, and Communication. Expressive language was more compromised than receptive language, nevertheless receptive abilities were also impaired. 39.5% of the sample presented with Autism Spectrum Disorder (ASD). By stratifying CdLS phenotypes by genetic, NIPBL mutated individuals demonstrated a worse trend in cognitive functioning, in communication expressive skills, in motor skills and in ASD symptoms in comparison with the Clinical Diagnosis Group. Individuals with non-Truncating mutation (mostly missense) displayed better abilities in Communication and in relational aspects with no ASD while Truncating individuals presented with worse abilities in Daily Living Skills, Socialization, Motor Skills, and Communicative abilities. Conclusions: These findings should increase our awareness of the strengths and weaknesses points in CdLS individuals to guide appropriate targeted management; interventions addressing communicative impairments represent a clinical priority in CdLS patients.